Biodegradable polyesters have significant potential for biomedical applications including tissue engineering, drug delivery, and biosensors. The most commonly used materials for these applications have been poly(L-lactic acid) (PLLA), poly(glycolic acid) (PGA), poly(ε-caprolactone) (PCL) and their copolymers (Wang, Y. et al., Nat. Biotech. 2002, 20, 602; Uhrich, K. E. et al., Chem. Rev. 1999, 99, 3181). However, many medical devices are implanted in dynamic environments of the body, which require elastomeric materials that will respond to these stresses. To minimize irritation of surrounding tissue, the material must be soft, resilient, and have similar mechanical properties. Furthermore, degradable materials are especially advantageous because they offer temporary mechanical support without the requirement of additional surgeries (Peppas, N. A.; Langer, R. Science 1994, 263, 1715).
The degradation kinetics of a material can be a strong function of the properties of the material, especially its morphology (Tm, Tg) and its topology (linear, branched, crosslinked). These parameters can affect the permeability of the material to reagents that can facilitate its degradation such as water and enzymes. Two general classes of these degradable polyester-based elastomers exist: thermoplastics and thermosets. While semicrystalline thermoplastics offer the advantage of ease of fabrication, they degrade heterogeneously due to the mixture of crystalline and amorphous regions. This can lead to rapid loss of mechanical properties as well as large deformation as the material degrades (Amsden, B. G. et al., Biomacromolecules 2004, 5, 2479). Conversely, amorphous thermosets offer more homogeneous degradation which leads to linear loss of mass and mechanical properties, as well as minimal deformation as the material degrades.
There are two general strategies toward preparing these amorphous thermoset elastomers. The first is to incorporate multifunctional monomers, such as glycerol or bis(ε-caprolactone-4-yl)propane (BCP), into the polymerization feed. Albertsson and Amsden have used both of these crosslinkers in ring opening polymerization (ROP) to form crosslinked PLLA and PCL containing materials (Palmgren, R. et al., J. Poly. Sci., Part A: Poly. Chem. 1997, 35, 1635; Palmgren, R. et al., J. Poly. Sci., Part A; Poly. Chem. 1997, 35, 1635; Amsden, B. G. et al., Biomacromolecules 2004, 5). Zhang, Tsutsumi, and Langer all provide examples of glycerol and sebacic acid based thermosets showing a wide range of mechanical and degradation properties (Nagata, M. et al., J. Poly. Sci., Part A: Poly. Chem. 1999, 37, 2005; Liu, Q. et al., J. App. Poly. Sci. 2005, 98, 2033). While the incorporation of multifunctional monomers provides a facile route to crosslinked materials, the resulting materials have very limited processing options.
The second approach to preparing these amorphous thermoset elastomers is to synthesize prepolymers containing reactive functional groups that can be subsequently crosslinked in a second step. This approach allows for the fabrication of materials using standard molding techniques, dramatically increasing the processing options of these materials. Amsden, Sepälä, and Storey all provide examples of crosslinking vinyl endgroup functionalized star-shaped PCL and PLLA prepolymers (Turunen, M. P. et al., Polym. Int. 2001, 51, 92; Storey, R. F. et al., Polymer 1997, 38, 6295). Nagata introduced aromatic cinnamic acid groups into the backbone of PCL to facilitate crosslinking in a second step (Nagata, M.; Sato, Y. Polymer 2003, 45, 87). Mikos has followed a similar strategy to prepare hydrogel materials (Jo, S. et al., Macromolecules 2001, 34, 2839). Fumaric acid was used to prepare unsaturated poly(ethylene glycol) PEG materials that were subsequently crosslinked using a radical initiator.
These examples of materials leave several issues to be addressed. First, the star-shaped materials all require added synthetic steps as the endgroups are functionalized postpolymerization. Second, nearly all of these prepolymers are semi-crystalline, limiting their effectiveness as good candidates for preparing elastomeric materials. Third, the concentration of hydrolysable ester groups in the hydrogel materials is relatively low, limiting the degradability of these materials. Finally, none of these examples provide a facile option for tuning the hydrophilic or hydrophobic properties of these materials, which affects water uptake and degradation rates.